Severe Acute Respiratory Syndrome (SARS) is a respiratory illness that has recently been reported in a number of countries. SARS first arose as a potential threat to human health in late 2002. It has been recognized as a newly emerging infectious disease that is highly contagious with significant morbidity and mortality. Originating in Southeast Asia, the virus has infected approximately 5,663 individuals in 26 countries around the world as of Apr. 30, 2003. M.M.W.R., 52(17):388-90 (May 2, 2003). Of these infections, 372 (approximately 6.6%) have resulted in fatalities. Id. SARS is a significant threat to the health and welfare of the human population worldwide, and efforts are currently underway to develop treatments for the disease.
SARS is generally characterized by an incubation period typically 2-7 days in length, with infected individuals typically exhibiting high fevers, sometimes with accompanying chills, headache, malaise and myalgia. The illness progresses with the onset of a dry, non-productive cough or dyspnea, accompanied by or advancing into hypoxemia. 10-20% of cases require intubation and mechanical ventilation. Furthermore, at the peak of respiratory illness, approximately 50% of infected individuals develop leukopenia and thrombocytopenia. M.M.W.R., 52(12):255-256 (Mar. 28, 2003).
The patterns by which SARS spreads suggests droplet or contact transmission of a viral pathogen. Poutanen et al., New England Journal of Medicine, published online Mar. 31, 2003, www.nejm.org. Recently, SARS has been associated etiologically with a novel virus, SARS-associated coronavirus (SARS-CoV), a member of the coronavirus family of enveloped viruses which replicate in the cytoplasm of infected animal host cells. Coronaviruses are generally characterized as single-stranded RNA viruses having genomes of approximately 30,000 nucleotides. Rota, P. A., et al., Sciencexpress, Published online May 1, 2003; 10.1126/science.1085952. Coronaviruses fall into three known groups; the first two groups cause mammalian coronavirus infections, and the third group causes avian coronavirus infections. Id. Coronaviruses are believed to be the causative agents of several severe diseases in many animals, for example, infectious bronchitis virus, feline infectious peritonitis virus and transmissible gastroenteritis virus, are significant veterinary pathogens. Id. These known coronaviruses cause only mild symptoms in humans.
SARS-CoV, has a genome of 29,727 nucleotides in length with 11 Open Reading Frames and a genomic DNA of 41% G-C. Id. Phylogenetic analysis reveals that SARS-CoV represents a new group of coronavirus, distinct from the previously known three groups of Coronavirus. Id. Sequencing of SARS-CoV isolates from infected patients in other locations worldwide confirms this distinct grouping. Marra, M. A., et al., Sciencexpress, Published online May 1, 2003; 10.1126/science.1085953. In contrast to the three known groups, SARS-CoV causes the severe disease in humans described above.
Recent studies have examined the virulence of SARS-CoV. According to the World Health Organization, SARS-CoV is stable in feces at room temperature for at least 1-2 days, and is stable in stool from diarrhea patients for approximately 4 days. Additionally, SARS-CoV was stable in cell-culture supernatant with minimal reduction in virus concentration after 21 days at 4° C. and −80° C., and SARS-CoV lost only one log of virus concentration at stable room temperature for 2 days in cell-culture supernatant. SARS-CoV does demonstrate susceptibility to commonly used disinfectants and fixatives. WHO Data on Stability and Resistance of SARS. However, the data strongly suggest that SARS-CoV is capable of retaining virulence outside of human hosts for protracted periods of time.
In addition to SARS-CoV, other infectious agents are suspected of being implicated in SARS. For example, a human metapneumovirus has also been isolated from patients suffering from SARS. Poutanen et al., New England Journal of Medicine, published online Mar. 31, 2003, www.nejm.org. It is possible that a combination of pathogens is responsible for SARS. It is also possible that SARS involves an opportunistic infection by a secondary pathogen or multiple secondary pathogens.
As of Mar. 25, 2003, the U.S. Centers for Disease Control and Prevention stated that “[n]o specific treatment recommendations can be made at this time.” CDC SARS Treatment, www.cdc.gov/ncidod/sars/treatment. One therapy currently administered in Hong Kong, a combination of steroids and the antiviral agent ribavirin, has been criticized as ineffective and even dangerous to recipients. D. Cyranoski, Nature, 423:4 (2003). Other attempted therapies have included administration of antibiotics or oseltamivir. Poutanen et al., New England Journal of Medicine, published online Mar. 31, 2003, www.nejm.org. In the absence of an effective treatment, healthcare workers are limited to using supportive measures, such as intravenous (IV) fluids, oxygen and, when necessary, mechanical ventilation and intubation, to treat patients having SARS.
Various measures have been attempted in an effort to control the spread of SARS. These measures include travel restrictions/advisories, quarantines, SARS-specific screening in health care settings and increased education of the public regarding proper infection-control procedures. Precautions such as respirators, gloves, goggles and gowns are being recommended for clinicians and health care workers to help limit the spread of SARS. While a few countries have reported that the spread of the disease has peaked, in other countries, such as China, SARS continues to spread uncontrollably.
Experts predict that a vaccine for the disease is unlikely to be available for a number of years. Indeed, according to the top infectious disease scientist for the United States government, “several years” of accelerated research will be required before a vaccine is generally available. Nesmith, New York Times Syndicate; Published online Apr. 7, 2003; www.nlm.nih.gov/medlineplus/print/news/full story—12280.html. Further, the ability of coronaviruses to rapidly mutate could provide a substantial obstacle to the development of an effective vaccine. Moreover, even if a vaccine is developed, the vaccine may comprise the immunity of a patient and actually worsen the immune response to SARS. Thus, the disease remains a significant threat to the world population and appears likely to do so for quite some time.
Accordingly, a need exists for an effective treatment for patients diagnosed with SARS, patients infected with an infectious agent associated with SARS, such as patients infected with SARS-CoV, or patients at imminent risk of contracting SARS, such as individuals that were exposed, or probably will be exposed in the near future, to an infectious agent associated with SARS.